Targeting CD19 in Diffuse Large B-Cell Lymphoma: Treatment Updates - Episode 3

L-MIND and RE-MIND Practical Implications

September 24, 2020
Targeted Oncology

Gilles A. Salles, MD, PhD: This combination is appearing in a field that has seen many new options becoming available for the treatment of our patients. We have seen CAR [chimeric antigen receptor] T-cell therapy being available now for a certain time, and have appreciated how the initial results observed in the phase 2 study, leading to drug approval of 2 of these CAR T products, has been confirmed in the real world, both in terms of efficacy but also safety. As we know, these are agents that are highly effective in the third line of therapy, with response rates ranging from 55% to 80% and complete response rates from 35% to 45%. Again, those patients who achieved a complete response experienced a very prolonged complete response, the majority of them being still without disease progressions at about 2 years.

It’s a complex treatment, we all know that in terms of logistics, in terms of organizing the patient pathway from presentation, drug approval, insurance approval, apheresis, eventually using some bridging therapy and managing the very specific adverse effects that are associated with CAR T. But it’s obviously a very promising treatment. Right now it’s available in the third line of therapy outside of clinical trial. There are trials investigating using it in the second line of therapy. And we’ll see in the near future how this CAR T-cell treatment goes, in addition to new approval probably of further CAR T-cell products.

Besides CAR T cells, there are also new agents. We have polatuzumab vedotin, which has been approved in combination with bendamustine/rituximab as a third-line regimen for patients with DLBCL [diffuse large B-cell lymphoma], as well as selinexor, the first XPO1 inhibitor, a nuclear export protein, which has been approved based on the response rate that was observed in this difficult-to-treat population.

We have new agents, and the question is how do we sequence these products. There are theoretical concerns regarding the expression of CD19 that can be eventually modulated. We do know that patients who failed CAR T-cell therapy, about one-third or more of them have lost CD19 [expression]. CD19 loss has not been described after tafasitamab. There have been anecdotal reports regarding the use of CAR T after tafasitamab, but we obviously need to consider how to sequence these possible therapies for our patients. And I won’t have a definitive answer for that, although we need to consider which one will be available for our patients. More specifically, I think that for patients with a rapidly growing tumor, it’s sometimes difficult to wait and organize the treatment with CAR T. We have to bridge the patient, while the combination of tafasitamab/lenalidomide is ready, off the shelf, and can be can be administered quite easily.

So I think it’s an important combination, and I think this regimen is particularly suitable for patients in whom we want to avoid specific toxicity by repeating chemotherapy, avoiding CAR T cell, but also in general for patients who have a disease in its first relapse after a disease-free interval after the first treatment. That doesn’t prevent us from using this regimen in second line or in early refractory patients, but this is probably the optimal population for the use of this combination.

I thank you for your attention and participation in this activity.

Transcript edited for clarity.